Preparation of o, o-dialkyl o-para nitrophenyl thiophosphate esters



Patented Dec. 22, 1953 UNITED STATES OFFICET 3191.RA'v I(.)l v OE'S QO-D LKY AR v NITRQBHENYI;THIOPHOSPHATEES ERS I Michael: N; :Dvcrnikofi, St; Louis, and 1 Evan J. Youilaytvalley .Park,tMo., assignors, totMonsantoi Chemical :Gomnana; Louis, M a comer tionofiDelaware No'Drawing. Application 'May 16, 1949,

' seri l No. 93,634

.12 Claims. (Cl. 260- 4461),

This invention-relates 120 organic .thiophosphate" estens; moreparticularly it .relates to. animpmved commercially ,feasibleiprocess :forthelpreparation of 0,0.-diall -:yl.:'O-p-mitrophenyl;ithiophosphata esters of the generalzformula'z- 1 This particular prooess=resultsirr'low yields and is extremely hazardous.- In order- 120 prepare the suspension of sodium p nitrophenate in mono chlorobenzene, it is necessary. to add p-nitrophenol to monochlorobenzene, neutralize with asolu tion of: sodium hydroxide and subsequently dehydrate by an :azeotropi'e distillation of the-monochlorobenzene and water: I During distillation there'is a tendency-for thesodium p-nitrophenate to lump and-besubj-eoted -to local overheating.

This localoverheating at times'oauses the sodium p-nitrophenate tmdecompose violently thereby making commercial: preparation ;oi this suspen-a sionhazardousamtundesirable; It is anobject -otthis'invention 'to provide a process-for the preparation; of organic thiophosphate esters.

It'is a furthenobj-eotof this invention to pro vide an improved commercially 'feasible proeess for thepreparation of organic thiophosphate esters wherein the hazard=conneoted with the use- 5- of an alkali metal pnitr ophenate is red'uoed toe minimum It is also an 0103 eet ot' this invention to providex an improvedcommescially -f'easible process :fon

the preparation-ofibrg-anib thiophosphate esters in which process these-esterseareobtained ini highi yields.

Further;objectsewilleheoome apparent-efrom the;

descrintion o the essa d-theolaimsi:

plished by; .thexxapplicant's novel" process which comprises preparing. the? dialkoxythioph'osphoryl chloride in the-normaI-manner and reacting the dialkoxythiophosphoryl chloride-with an alkali metal p nitrophenate'; inrz'an alcoholic medium;- This reaction maybe: carried out, in several ways.

To the dialkoxythiophosphoryl chlorideprepared in: the normal. manner: may 1be added p-nitrophenol and subsequently'an alcoholic: solution of analgkali metal'alkylate, thereby-forming in situ an alkali metal p-nitrophenate? which reacts on formation with the;dialkoxythiophosphoryl,chlo;-. ride. to form the organiathiophosphate' ester in high yields. The reaction in'ayalso; be carried: out by reacting dialkoxythiophosphoryl; chloride with an alkali metal p-nitrophenate contained in an alcoholic medium.

t m l'e' I 13083.1 pounds ofthiophosphoryl chloride was added, over a period oi two tothree hours, 350,5 pounds or"; an approximately.2 0% solution of sodi, um. late. i e hyl alco ol, ma nt i h temperature below 10 (3.; Iothis mixture was then added 68.2 pounds-of p-nitrophenoLand to this, resulting solution -was i added, over a period of one to twohours, 166.9 pounds of an approxie mate1y-20% solution of sodium ethylate in ethyl alcohol, maintaining the temperature below 10 C. This reaction masswasagitated by mechanical stirring, forapproximately 18 hours at the end of which timethereaction was-complete.

A larger portion of the ethyl alcohol in the batch was distilledfrom-v-the stirred. batchat atmospherio pressure. To the reaction mixture was then added 47-gallonsof. water: in order to-dissolvesodium. chloride andto separate the 0pdiethyl O-p -nitrophenyl; thiophosphate from the, residual alcohol.-v The resulting mixture was p m d: th ou h a r.- -c atedfi ter n c r t m e sums The I Ia eW s allowed. to s parate into an u per aqueous layer ic was d cantedfrom: the. lowerfllayer, of 0-,O- :ii thyl 01 nitrophe yl. thi phosimate,

The l wer. layer was ttwicerwashe by. stirring with -15: gallons oia 3%:aqueoussolut n f i umcarbonate w ich-was followed-b o e l sal lon-watenwasm heawet owerf lay e was th n-sub cted o steam d stillat on 'phate. U The distillation :twas-continu d: un l no.-

to'remove t et yl; t ph sei moreoilrwas'notioed in the: distillate.

Thezwater layeitzwasdecanted: from the cooled= material inethe' still DQlha The-organic layercwas The objects; zotl tth sreinyenticneiaiteeaooome; dried by heatinsz td llfl-fiflz nude: mm;-.vacuaces mi 3 um for hour. The finished product, 0,0-diethyl O-p-nitrophenyl thiophosphate, was obtained in an over all yield of 70% based on thicphosphoryl chloride.

The 0,0-diethyl O-p-nitrophenyl thiophosphate thus obtained was a dark brown oily liquid, having a crystallizing point of 3.4 C., a specific gravity of 25/25 of 1.2651 and a 11. C. of 1.537, Y While specific quantities and temperatures have been set forth in Example I, it is not intended that the scope of the novel process of this invention be limited solely to these expressed quantities and temperatures. Thus, for example, while 2.0 to 2.2 mols of sodium alkylate, the sodium salt of an alkyl alcohol containing at least 1 and not more than 8 carbon atoms, to 1 mol of thiophosphoryl chloride is illustrative of the preferred range of quantities of reactants for the formation of dialkoxythiophosphoryl chloride, greater or lesser amounts of sodium alkylate may be utilized. However, if greater than 2.2 mols of sodium alkylate are'used excessive quantities of trialkyl thiophosphate are formed and if less than 2.0 mols of sodium alkylate are used ex cessive quantities of alkoxythiophosphoryl dichloride are formed.

The concentration of sodium ethylate in ethyl alcohol may also be considerably varied. However, if the concentration of sodium ethylate is increased significantly above 20%, sodium ethylate tends to crystallize from the alcohol solution. If the concentration is reduced below 20%, the reaction may still be carried out. However, provision must be made for the increased quantities of solution required.

The reactions are best carried out at a temperature in the range of from about -l C. to about C. Temperatures in excess of 10 C. promote the formation of trialkyl thiophosphate. If the temperature is reduced below -10 C., the reaction necessarily proceeds slower. However, in the reaction between dialkoxythiophosphoryl chloride and the alkali metal para-nitrophenate in an alcoholic medium, a temperature within the preferred range of from about -l0 C. to about 10 C. need be maintained only during the time that the alkali metal p-nitrophenate in an alcoholic medium is being added to the dialkoxythiophosphoryl chloride. Subsequent to the addition of the reactants, the temperature may be raised even to the boiling point of the more volatile component.

The reactants, namely, thiophosphoryl chloride, alkyl alcohol solution of sodium alkylate and p-nitrophenol, should be substantially anhydrous with a moisture content of preferably less than 0.3% by weight. By maintaining substantially anhydrous conditions, it is possible to recover substantially anhydrous alcohol from the reaction, which may be recycled without further dehydration and used to prepare additional quantities of an alkyl alcohol solution of sodium alkylate. In order that commercially feasible yields be obtained, however, it is not absolutely necessary that substantially anhydrous conditions be maintained during the reaction between dialkoxythiophosphoryl chloride and the sodium pnitroplienate in an alcoholic medium. Thus, in this last step of the reaction, it is possible to utilize an alcoholic medium that may contain as much as by weight of water. Furthermore, in this latter step the alkali metal pnitrophen ate in an alcoholic medium could be prepared by reacting p-nitrophenol with sodiumncarbon -p-nitrophenatewill remain-unreacted- 4 ate, potassium hydroxide, potassium carbonate, or sodium hydroxide in an alcoholic medium. thereby forming an aqueous alcoholic solution or suspension of an alkali metal p-nitrophenate. Utilizing such a n'ietliod of preparation of the alcoholic solution of the alkali metal p-nitrophenate does not permit the recovery of substantially anhydrous alcohol from the reaction. In such a case, therefore, the recovered alcohol must be dehydrated before additional quantities of an anhydrous alkyl alcohol solution of sodium alkylate may be prepared and utilized in the preparation of dialkoxythiophosphoryl chloride, which reaction is best carried out under substantially anhydrous conditions according to the process as described herein. I

While it is more economically feasible to utilize the same sodium alkylate solution in the corresponding alcohol in both the reaction for the formation of dialkoxythiophosphoryl chloride and the final reaction for the formation of dialkyl p-nitrophenyl thiophosphate, a diiferent alcohol solution of a different sodium alkylate may be utilized in the latter reaction. Thus, in the formation of sodium p-nitrophenate in situ in Example I, a solution of sodium butylate in butyl alcohol could have been utilized. However, inasmuch as the alcohol recovered from the latter reaction is substantially anhydrous and may be re cycled for the preparation of additional quantities of sodium alkylate, it is preferable to utilize the same alcohol and sodium alkylate in the latter reaction as was used in the first reaction.

lhe order of adding the reactants in the above mentioned step of the novel process of this invention is to a certain degree of significance, It is preferred that the reactants be added so as not to have present a mixture of dialkoxythiophosphoryl chloride and an alcohol solution of sodium alkylate without the added presence of p-nitrophenol in such a quantity that the molecular proportion of p-nitrophenol present approaches or exceeds the molecular proportion of sodium alkylate present in the mixture. Thus, while in Exam- 7 pic I is illustrated the preferred procedure for carrying out this reaction, that is the formation of sodium p-nitrophenate in situ, it is not intended that the applicants invention be solely limited to this procedure. It has been found that equally good yields and purity of product may be obtained by adding the p-nitrophenol and alcohol solution of sodium alkylate simultaneously to the dialkoxythiophosphoryl chloride. Furthermore, the alcoholic solution of sodium p-nitrophenate may be prepared separately by adding a 1 molecular proportion of p-nitrophenol to a substantially 1 molecular proportion of sodium alkylate in an alcohol solution and reacting the thus formed sodium p nitrophenate contained in an alcoholic medium with dialkoxythiophosphoryl chloride either by adding the alcoholic solution of sodium p-nitrophenate to the dialkoxythiophosphoryl chloride or by adding diallioxythiophosphoryl chloride to the alcoholic solution of sodium p-nitrophenate.

It is preferred that p-nitrophenol be used in the ratio of approximately a one molecular proportion of the amount of thiophosphoryl chloride initially utilized. However, the amount may be varied to some extent. If the amount of p-nitrophenol is substantially decreased, the desired reaction may not be completed. If the quantity of p-nitrophenol is substantially increased, ex-

cessive quantities of p-nitrophnol or sodium zatcafzai .-::'It is, also preferredthat sodium alkylatab rused in the ratio of approximately;,onemoleculareproe portion ,to the; amount :OfgjIkIIj-tlODhCIlOl utilized.

- However, theamounamay beyaried- .tohsomevex- .tent. .,If.,the amount; of sodium-,alkylate is; sub- .stantially increased over-the preferredv proportion, excessive quantities sof ;tr ialkyl thiophosphate. are iormedafiectingthe yield:of.;the ifinal product. Ii substantiallyalesser quantitiestar used the yield otthe': final 1productrwill ;1,)B;:.decreased as all ,of thegdialkoxythiophosphoryl chloride will not .have:.react ed; .to: form; Q,L .ethy1 o-p-nitrophenyl thiophosphate.

"Example I-I To. 1: mol of thiophosphoryl chloride in .a suitable reactor was added over a period. oftwohours .2.05, mols of sodium methylate contained as a 20 solution ;-in methyLalcohol, maintainin -the temperature below C. To this;-mixture -was added" 1 mol of pnitrophenol and. to the resultvLing-solution was then added. over a period of, 1

hour, 1 mol of sodium -methylate contained in a solution of methyl-alcohol, maintaining the temperature below 10 C. Stirring was continued for 16 hours at which timethereaction was complete.

Approximately of theexcessmethyl alcov.hol was distilled. at atmospheric pressure from the stirred batch. ;The batch was then washed with water, filtered and decanted. Thelower layer was twicewashed with a 3% aqueous solution of'sodium carbonate; followed by another water wash. The-wet lower layerzwas subjected to steam distillation until :no more oil waswnoticed being carried over in the: distillate. j'Ihe water layer was decanted' from, the: organic; ma-

terial and thepfinished product; 0,0-dimethyl O-.p nitrophenyl thiophosphate rwas :dried by heating to 110 C. under mm. vacuum for 40 A hour.

7 Example III To 1 mol of thiophosphoryl chloride contained in a-suitab1e reactorwasadded 2.2 mols-of sodium butylate contained asa 20% solution of sodium butylate in butanol. The temperature was maintained below 10 C. during the-addition periodwhich extended over a -period of 3 hours. To this reaction mass was added one mol of anhydrous sodium p-nitrophenatecontained as a 20% solution in butyl alcohol. During this addition period which extended over a period of 2 hours, thetemperature was maintained. below 10 C. The mixturewas agitated for 16 hours at which time the reaction was complete.

Excess butanol was distilled from the batch at atmospheric pressure. The resulting reaction mass was further purifiedin accordance with the procedure outlinedin Example ,II. The resultant product was 0,0-dibuty1'O-p-nitrophenyl thiophosphate.

Example IV To 1 mol of thiophosphoryl chloride was added, over aperiod of 3 hours, 2.1 molsof sodium 2-ethylhexylate contained as a'l0 %-,solution -of sodium Z-ethylhexylate in 2:ethylhexanol, maintainingthe temperature .below .10". ,C. ;To. this mixture wasadoled 1' mol of p-nitrophenol and subsequently, over a period of 2 hours, 1 molof sodium 2-ethylhexylate contained as a. 10%;;s0- lution in 2-ethylhexanol. The mixture was agitated for 16 hours at which time thereaction was complete.

aExcesst2-etbrlhexa i9 t asnzemovedrbmdist lation-; un er;reduced Jlhe:rea.cti9.r1 1 Wa e .:a V. 3%

- aque us Q II Q iQfiSQd U-m carbo ate- .The: W a oduct:wasrsubiected lac-steam distilla ion- ..T.h water. :lay rvwasztd lcanted from :th i cooled; maerial land-the i rsani The resultant ;product;-.was- .O, O.-.di=2-.i-ethylheXy 0:1 eni rophenylthiophosphate.

Example -V To 83.1 lbs. of thiophosphoryl chloride was added, over-a period of-2'- to- 3. hours, 350.5 lbs. of an approximately*20% solutionof sodium eth- .y1ate ethyl alcohol, maintaining a. temperature below 10-TC. .To this mixture was then add- 7 ed. 68.2 lbs. ,of ..p-nitrophenol and 19.6 .lbs. ,of

fiakedsodium hydroxide. The reaction mass .was agitated .until the. reaction. was. complete.

A large portion. of the..ethyl alcohol inthe batch was distilled fromthebatchat atmospheric pressure. Water-was then added to, the reaction mixture to dissolve sodium chloride and to separate the thiophosphate.esterfromthe alcohol. After filtering to remove.gumsLtheUfiltrate was allowed to separate into. an .upperaqueous layer which was decanted .from. the lower layer .of

. 0.0-, diethyl .O.-,p.-nitr9phenyl. thiophosphate.

The lower-layer was washed vwith.a33%,,aqueous solution of.sodium carbonateandwater. The wet lower layer. was then subjected, to steamdistillation to remove triethylthiophosphate. The wet ester was recovered and dried by heating at about C. under-vacuum,,thereby obtaining substantially pure 0,0-diethy1 O-p-nitrophenyl thiophosphate inexcellent yield.

. ExamnlaVI Over a period of-several"hours,' 350*lbs. of an approximately 20 solutioncof sodium ethylate in ethyl alcohol "was added to'83"l'bs. of thiophosphoryl ohloridewhile maintaining a-temperature below about 10? C. To thismixture was then added'68 lbs. of penitrophenol -and"52.0 lbs. of sodium carbonatewhilemaintaining a temperature below abouti10 C. Afterall the reactants had been ad-ded,;the temperature was raised to about 80 C. and agitated by' mechanical stirring until the reaction was complete.

Excess ethyl alcohol, was removed by 'distilla wherein R representsarr alkylradical containing at least land not .morethan 8,.carbon atoms, the step. comprising.maintainingtreaction temperatures within the range of about 10 C. to +10 C. while adding together in an alkyl alcoholic medium substantially equimolecular proportions each of (1) dialkoxythiophosphoryl chloride wherein each alkyl substituent contains at least 1 and not more than 8 carbon atoms, (2) p-nitrophenol, and (3) sodium alkylate containing at least 1 and not more than 8 carbon atoms, said sodium alkylate being added as a solution of sodium alkylate in alkyl alcohol.

2. In a process for the preparation of 0,0-dialkyl O-p-nitrophenyl thiophosphate esters represented by the formula wherein R represents an alkyl radical containing at least 1 and not more than 8 carbon atoms, the step comprising maintaining reaction temperatures Within the range of about l C. to +10 C. during the simultaneous addition of substantially equimolecular proportions each of p-nitrophenol and sodium alkylate to an alkyl alcoholic medium containing an equimolecular proportion of dialkoxythiophosphoryl chloride, wherein each alkyl substituent of said dialkoxythiophosphoryl chloride contains at least 1 and not more than 8 carbon atoms, and said sodium alkylate contains at least 1 and not more than 8 carbon atoms and being added as a solution of sodium alkylate in alkyl alcohol.

3. In a process for the preparation of 0,0-dialkyl O-p-nitrophenyl thiophosphate esters represented by the formula a-o s R-0/ wherein It represents an alkyl radical containing at least 1 and not more than 8 carbon atoms, the step comprising maintaining reaction temperatures Within the range of about 10 C. to +10 C. during the addition of a substantially equimolecular proportion of sodium alkylate to an alkyl alcoholic medium containing substantially equimolecular proportions each of p-nitrophenol and dialkoxythiophosphoryl chloride, wherein each alkyl substituent of said dialkoxythiophosphoryl chloride contains at least 1 and not more than 8 carbon atoms, and said sodium alkylate contains at least 1 and not more than 8 carbon atoms and is added as a solution of sodium alkylate in an alkyl alcohol.

4. In a process for the preparation of 0,0-diethyl O-p-nitrophenyl thiophosphate, the step comprising maintaining reaction temperatures within the range of about 10 C. to +10 C. during the addition of a substantially equimolecular proportion of sodium alkylate to an alkyl alcoholic medium containing substantially equimolecular proportions each of p-nitrophenol and diethoxythiophosphoryl chloride, said sodium alkylate containing at least 1 and not more than 8 carbon atoms and being added as a solution of sodium alkylate in alkyl alcohol.

5. In a process for the preparation of 0,0-diethyl O-p-nitrophenyl thiophosphate, the step comprising maintaining reaction temperatures within the range of about -10 C. to +10 C. during the addition of a substantially equimolecular proportion of sodium ethylate to an ethyl alcohol solution of substantially equimolecular proportion each of p-nitrophenol and diethoxythiophosphoryl chloride, said sodium ethylate being added as a solution of sodium ethylate in ethyl alcohol.

6. In a process for the preparation of 0,0-dibutyl O-p-nitrophenyl thiophosphate, the step comprising maintaining reaction temperatures within the range of about 10 C. to +10 C. during the addition of a substantially equimolecular proportion of sodium alkylate to an alkyl alcoholic medium containing substantially equimolecular proportions each of p-nitrophenol and dibutoxythiophosphoryl chloride, said sodium alkylate containing at least 1 and not more than 8 carbon atoms and being added as a solution of sodium alkylate in alkyl alcohol.

7. The process of claim 6, wherein sodium alkylate is added as a solution of sodium butylate in butyl alcohol.

8. The process of claim 6, wherein sodium alkylate is added as a solution of sodium ethylate in ethyl alcohol.

9. In a process for the preparation of 0,0-di- 2-ethylhexyl O-p-nitrophenyl thiophosphate, the step comprising maintaining reaction temperatures within the range of about -10 C. to +10 C. during the addition of a substantially equimolecular proportion of sodium alkylate to an alkyl alcoholic medium containing substantially equimolecular proportions each of p-nitrophenol and di 2 ethylhexoxythiophosphoryl chloride, said sodium alkylate containing at least 1 and not more than 8 carbon atoms and being added as a solution of sodium alkylate in alkyl alcohol.

10. The process of claim 9, wherein sodium alkylate is added as a solution of the sodium 2- ethylhexylate in Z-ethylhexyl alcohol.

11. In a process for the preparation of 0,0- dimethyl O-p-nitrophenyl thiophosphate, the step comprising maintaining reaction temperatures within the range of about 10 C. to +10 C. during the addition of a substantially equimolecular proportion of sodium alkylate to an alkyl alcoholic medium containing substantially equimolecular proportions each of p-nitrophenol and dimethoxythiophosphoryl chloride, said sodium alkylate containing at least 1 and not more than 8 carbon atoms and being added as a solution of sodium alkylate in alkyl alcohol.

12. The process of claim 11, wherein sodium alkylate is added as a solution of sodium methylate in methyl alcohol.

MICHAEL N. DVORNIKOFF. EVAN J. YOUNG.

References Cited in the file of this patent UNITED STATES PATENTS Number Name Date 2,471,464 Toy May 31, 1949 2,520,393 Fletcher Aug. 29, 1950 2,575,224 Manske Nov. 13, 1951 OTHER REFERENCES Schrader, B. I. O. S. Report 1808, Oct. 4, 1948, pages 7-13.

Fletcher etal.. J. Am. Chem. 800., vol. 70, pages 3943-44 (1948).

Thurston, Field Information Agency Technical Final Report 94.9, Tech. Ind. Intelligence Div., U. S. Dept. of Commerce, Oct. 14, 1946, pages 19 and 120. (Received U. S. Patent Office Jan. 20, 1948; released May 30, 1947). 

1. IN A PROCESS FOR THE PREPARATION OF O,O-DIALKYL O-P-NITROPHENYL THIOPHOSPHATE ESTERS REPRESENTED BY THE FORMULA 